KOACT Tablet

Co-amoxiclav oral preparations are indicated for short-term treatment of bacterial infections at the following sites when amoxicillin resistant beta-lactamase-producing strains are suspected as the case. In other situations, amoxicillin alone should be considered.

- Upper Respiratory Tract Infections (including ENT) in particular sinusitis, otitis media, recurrent tonsillitis. These infections are often caused by Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pyogenes.

- Lower Respiratory Tract Infections in particular acute exacerbations of chronic bronchitis (especially if considered severe), bronchopneumonia. These infections are often caused by Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis.

- Genito-urinary Tract and Abdominal Infections in particular cystitis (especially when recurrent or complicated - excluding prostatitis), septic abortion, pelvic or puerperal sepsis and intra-abdominal sepsis. These infections are often caused by Enterobacteriaceae (mainly Escherichia coli), Staphylococcus saprophyticus, Enterococcus species.

- Skin and Soft Tissue Infections in particular cellulitis, animal bites and severe dental abscess with spreading cellulitis. These infections are often caused by Staphylococcus aureus, Streptococcus pyogenes and Bacteroides species.

Mixed infections caused by amoxicillin-susceptible organisms in conjunction with Co-amoxiclav-susceptible beta-lactamase-producing organisms may be treated with co-amoxiclav. These infections should not require the addition of another antibiotic resistant to beta-lactamases.

Posology and method of administration

Since both the 375mg and 625mg tablets of Co-amoxiclav contain the same amount of clavulanic acid (125mg), two 375mg tablets of Co-amoxiclav are not equivalent to one 625mg tablet of Co-amoxiclav; therefore, two 375mg tablets should not be substituted for one 625mg tablet.

Adults

The usual adult dose is one 625mg tablet of Co-amoxiclav every 12 hours or one 375mg tablet every 8 hours. For more severe infections and infections of the respiratory tract, the dose should be one 1000mg tablet every 12 hours or one 625mg tablet every 8 hours.

(Please see the package insert about the details below.)

- Patients with impaired renal function

- Hemodialysis patients

Pediatric Patients

Pediatric patients weighing 40kg or more should be dosed according to the adult recommendations.

Due to the different amoxicillin to clavulanic acid rations in the 375mg tablet of Co-amoxiclav(250/125) versus the 250mg chewable tablet of Co-amoxiclav (250/62.5), the 375mg tablet of Co-amoxiclav should not be used until the pediatric patients weighs at least 40kg or more.

Administration

Co-amoxiclav may be taken without regard to meals: however, absorption of clavulanate potassium is enhanced when Co-amoxiclav is administered at the start of a meal. To minimize the potential for gastrointestinal intolerance, Co-amoxiclav should be taken at the start of a meal.

Penicillin hypersensitivity. Attention should be paid to possible cross-sensitivity when beta-lactam antibiotics, e.g. cephalosporins.

A previous history of Co-amoxiclav or penicillin-associated jaundice/hepatic dysfunction.

Gastrointestinal reactions:

Diarrhoea, indigestion, nausea, vomiting, and mucocutaneous candidiasis may occur. Antibiotic-associated colitis (including pseudomembranous colitis and haemorrhagic colitis) may occur rarely. Nausea, although uncommon, is more often associated with higher oral dosages. If gastrointestinal side effects occur with oral therapy they may be reduced by taking Co-amoxiclav at the start of meals.

Superficial tooth discolouration may occur rarely, mostly with the suspension. It can usually be removed by brushing.

Renal and urinary tract disorders:

Crystalluria occurs very rarely.

Gastro-urinary effects:

Vaginal itching, soreness and discharge may occur.

Hepatic effects:

Moderate and asymptomatic rises in AST and/or ALT and alkaline phosphatases occurs occasionally. Hepatitis and cholestatic jaundice occurs rarely. These hepatic reactions occurs more commonly with Co-amoxiclav than with other penicillins.

After Co-amoxiclav hepatic reactions occurs more frequently in males and elderly patients, particularly those over 65 years. The risk increases with duration of treatment longer than 14 days. These reactions may occur very rarely in children.

Signs and symptoms usually occur during or shortly after treatment but in some cases may not occur until several weeks after treatment has ended. Hepatic reactions are usually reversible but they may be severe and very rarely deaths occurs.

Hypersensitivity reactions:

Urticarial and erythematous skin rashes sometimes occur. Rarely erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative dermatitis, acute generalised exanthematous pustulosis (AGEP), serum sickness-like syndrome and hypersensitivity vasculitis occurs. Treatment should be discontinued if one of these disorders occurs. In common with other beta-lactam antibiotics angioedema and anaphylaxis occurs. Interstitial nephritis can occur rarely.

Haematological effects:

As with other beta-lactams transient leucopenia (including neutropenia and agranulocytosis), thrombocytopenia and haemolytic anaemia occurs rarely. Prolongation of bleeding time and prothrombin time also occurs rarely.

CNS effects:

CNS effects occurs very rarely. These include reversible hyperactivity, dizziness, headache and convulsions. Convulsions may occur with impaired renal function or in those receiving high doses.

(Please see the package insert about the details below.)

- In patients on anticoagulation therapy

- Other broad-spectrum antibiotics

- Allopurinol

Pregnancy

Treatment with Co-amoxiclav may be associated with an increased risk of necrotising enterocolitis in neonates. As with all medicines, use should be avoided in pregnancy, especially during the first trimester, unless considered essential by the physician.

Lactation

Co-amoxiclav may be administered during the period of lactation. With the exception of the risk of sensitisation, associated with the excretion of trace quantities in breast milk, there are no known detrimental effects for the breast-fed infant.

Changes in liver function may occur in some patients receiving Co-amoxiclav. The clinical significance of these changes is uncertain but Co-amoxiclav should be used with caution in patients with evidence of hepatic dysfunction.

Cholestatic jaundice, which may be severe, but is usually reversible, may occur rarely. Signs and symptoms may not become apparent for several weeks after treatment has ceased.

In patients with renal impairment, dosage should be adjusted according to the degree of impairment.

In patients with reduced urine output, crystalluria may occur very rarely, predominately with parenteral therapy. During the administration of high doses of amoxicillin, it is advisable to maintain adequate fluid intake and urinary output in order to reduce the possibility of amoxicillin crystalluria Serious and occasionally fatal hypersensitivity (anaphylactoid) reactions may occur in patients on penicillin therapy. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity.

Erythematous rashes have been associated with glandular fever in patients receiving amoxicillin.

Prolonged use may also occasionally result in overgrowth of non-susceptible organisms.

Co-amoxiclav is an antibiotic agent with a notably broad spectrum of activity against the commonly occurring bacterial pathogens in general practice and hospital. The beta-lactamase inhibitory action of clavulanate extends the spectrum of amoxicillin to embrace a wider range of organisms, including many resistant to other beta-lactam antibiotics.

Bacterial enzymes that destroy the antibiotic before it can act on the pathogen cause resistance to many antibiotics. The clavulanate in Co-amoxiclav anticipates this defence mechanism by blocking the beta-lactamase enzymes, thus rendering the organisms sensitive to amoxicillin’s rapid bactericidal effect at concentrations readily attainable in the body.

Clavulanate by itself has little antibacterial activity; however, in association with amoxicillin as Co-amoxiclav, it produces an antibiotic agent of broad spectrum with wide application in hospital and general practice.

Co-amoxiclav is bactericidal to a wide range of organisms including:

Gram-positive

Aerobes: Enterococcus faecalis*, Enterococcus foecium*, Streptococcus pneumoniae, Streptococcus pyogenes, Strepto-coccus viridans, Staphylococcus aureus*, Coagulase negative staphylococci* (including Staphylococcus epidermidis*), Coryne-bacterium species, Bacillus anthracis*, Listeria monocytogenes.

Anaerobes: Clostridium species, Peptococcus species, Peptostreptococcus.

Gram-negative

Aerobes: Haemophilus influenzae*, Moraxella catarrhalis* (Branhamella catarrhalis), Escherichia coli*, Proteus mirabillis*, Proteus vulgaris*, Klebsiella species*, Salmonella species*, Shigella species*, Bordetella pertussis, Brucella species, Neisseria gonorrhoeae*, Neisseria meningitides*, Vibrio cholerae, Pasteurella multocida.

Anaerobes: Bacteroides species* including B.fragilis.

*Some members of these species of bacteria produce beta-lactamase, rendering them insensitive to amoxicillin alone.